The macrophage has a number of seemingly contradictory functions as an immunoregulatory and effector cell. We have studied human monocyte function in several chronic granulomatous diseases (tuberculosis, sarcoidosis, schistosomiasis). Monocyte exert suppressor function which results in inhibition of T lymphocytes responses to specific antigens (TBC, schistosomiasis) or mitogens (sarcoidosis). The M phi also are activated during tuberculosis and show increased cytocidal activity for schistosomula and tumor targets as well as hyper-adherence to plastic. However, M phi effector function is decreased in some patients with schistosomiasis which may predispose to increased intensity of infection or to disease. In this project we have used in vitro inflammatory exposure of normal M phi to simplify and dissect alterations in disease states. Gram negative and tubercle bacillus products produce alterations in monocyte function which resemble in some but differ in other manners from changes attendant in disease. We propose to extend these observations to assess the role of cellular interactions in the generation and expression of M phi function. Particular attention will be placed on the mediators of physical interaction of M phi with lymphocytes and other targets and the macrophage products which may provide the basis for their function.